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P1‐151: Early onset of the impairment of neuroimmunoendocrine system in triple‐transgenic 3xTg‐AD mice
Author(s) -
Gimenez-Llort Lydia,
Vida Carmen,
Castro Núria M.,
Baeza Isabel,
Manassra Rashed,
La Fuente Mónica
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.701
Subject(s) - genetically modified mouse , spleen , immune system , medicine , endocrinology , basal (medicine) , oxidative stress , open field , glutathione , transgene , stimulation , biology , immunology , biochemistry , gene , insulin , enzyme
Background: Recently, we have reported gender-dependent neuroimmunoendocrine impairments in old 3xTg-AD mice and as compared to agematched non-transgenic mice. The aim of the present work is to determine the onset of the impairment of the neuroimmunoendocrine network and the oxidative status, that is, if it can be already observed at early stages of the disease. Methods: For this purpose, 4 month-old male 3xTg-AD mice and age-matched non-TgAD mice were studied. The screening included assessment of BPSD-like behaviours (in the corner, open-field and T-maze tests), weight of immunoendocrine tissues (spleen, thymus and adrenal glands) and several immune function parameters such as a natural killer activity (NK), lymphocyte proliferation in basal and stimulated conditions (Concanavaline A -ConAand Lipopolisaccharide -LPS-) and oxidative status by means of the total glutathione capacity (spectrophotometric assay of GSH), a relevant antioxidant in immune cells proliferation. Results: At 4 month of age, male 3xTg-AD mice exhibited increased neophobia, freezing behaviour, reduced exploratory efficiency and other behavioural variables indicative of reduced copying with stress strategies. The size of spleen was twice the normal size (both total weight and relative weight) while that of thymus and adrenal glands did not differed from the obtained in non-transgenic mice. The proliferative response to the mitogens in the spleen was decreased in transgenic mice with respect to the control group. Nevertheless, this impairment only reached statistically significance in the case of LPS stimulation. Furthermore, we have also seen that there was a trend of decrease in the NK activity and GSH in this organ, but these parameters did not show differences between genotypes. Conclusions: At early stages, 3xTg-AD mice show spleenic hypermegalia concurrent with a decrease in the lymphoproliferative response to mitogens and a decrease in GSH. The present results provide evidence that the impairment of immune fuctions, that we have already established in 3xTg-AD mice at the age of 15 months, becomes already apparent at 4 months of age (modeling early stages of the disease) and it is likely to be related to the reduced copying with stress strategies observed at this age.